Once considered a sacred herb in Celtic tradition, mistletoe has been used for centuries for conditions as diverse as high blood pressure, epilepsy, exhaustion, anxiety, arthritis, vertigo (dizziness), and degenerative inflammation of the joints.

Beginning in the early 20th Century, mistletoe came into practice in Europe as an anti-cancer therapy and this remains a source of great popular interest. For example, in Norway, mistletoe has been considered a "non-proven therapy" or NPT but has been used as a popular method for healing.

In the last 50 years, many laboratory, animal, and human studies have been conducted on potential anti-cancer effects thought to be caused by immuno-stimulatory effects of mistletoe.

The most promising potential use is as a cancer therapy, but there is still insufficient clinical evidence to consider it a proven cancer therapy. Toxic effects seem to be rare, but have been reported. The National Cancer Institute monograph "Mistletoe Extracts" provides a complementary and alternative medicine (CAM) information summary and overview of the use of mistletoe as a treatment for cancer, indicating that: [a] in animal studies mixed results have been obtained using mistletoe extracts for slowing tumor growth; [b] well designed clinical trials using mistletoe or its components have not been sufficient to prove efficacy in the treatment of human cancer(s); [c] mistletoe plants and berries are toxic to humans and their extracts are not sold in the United States.

Mistletoe is not commercially available in the United States, but two U.S. investigators currently have Investigational New Drug approval (IND) from the U.S. Food and Drug Administration (FDA) to study mistletoe.

The German Commission E Monographs list mistletoe as a treatment for degenerative inflammation of the joints and as palliative therapy for malignant tumors.

Two major types of mistletoe, European and American, contain very similar proteins and are reputed to have different uses. European mistletoe is believed to reduce blood pressure and act as an antispasmodic and calmative agent, while American mistletoe is believed to simulate smooth muscles, increase blood pressure, and trigger uterine and intestinal contractions. However, there is little research to substantiate any of these claims.

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

GRADE *

One retrospective case study documented potential benefits of mistletoe extract injection in the management of arthritis. Further research is needed before recommending for or against the use of mistletoe in the treatment of this condition, for which other more proven treatments are available.

C

Mistletoe is one of the most widely used unconventional cancer treatments in Europe. Extracts have been studied for many types of human cancers, including bladder, breast, cervical, central nervous system (CNS), colorectal, head and neck, liver, lung, lymphatic, ovarian, and kidney cancers, as well as melanoma and leukemia. However, mistletoe has not been proven to be effective for any one type of cancer. Larger, well-designed studies are needed before mistletoe can be recommended for cancer patients.

C

In a preliminary description in 1997, some patients achieved complete elimination of the virus after treatment with Viscum album although these studies were not well designed. A small exploratory trial investigated the effects of mistletoe on liver function, reduction of viral load and inflammation, and maintenance of quality of life by the immunomodulatory and/or cytotoxic actions of mistletoe extracts but little effect was seen. Larger, well-designed clinical trials are needed to resolve this conflicting data.

C

Treatment of HIV patients with mistletoe has been done in Europe since the beginning of the AIDS epidemic based on proposed immunomodulatory effects. Treatment seems to be tolerable with minimal side effects reported. Mistletoe may assist in inhibiting progression but not all mistletoe preparations have shown equal effects. Further study is needed before a recommendation can be made.

C

A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further study is needed to confirm these results.

C

Studies of Iscador® (conducted by the same authors) document improved clinical symptoms and markers of immune function in children with recurrent respiratory disease (RRD) exposed to the Chernobyl nuclear accident. There is insufficient evidence to recommend for or against mistletoe therapy for RDD in general.

C

* Key to grades

A: Strong scientific evidence for this useB: Good scientific evidence for this useC: Unclear scientific evidence for this useD: Fair scientific evidence for this use (it may not work)F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Traditionally, tea has been made with mistletoe leaves, hawthorn leaves and flowers, and lemon balm leaves in equal parts. Two cups daily has been prepared by infusing two teaspoons of the mixture for 5-10 minutes. Cold water infusions, dried aqueous extracts, and fluid extracts (1:1 in 25% alcohol) have been taken by mouth.

Mistletoe has been studied in multiple injectable regimens (intravenous, subcutaneous, intrapleural) and given by a healthcare provider in a controlled setting. Sometimes therapy includes an induction phase and a maintenance phase. Mistletoe should only be given by a qualified healthcare professional. No standard dose can be recommended at this time. Further research is needed as there are many potential side effects and interactions.

Children (under 18 years old)

Mistletoe has been studied in children for respiratory infections. Further research is needed before a recommendation can be made.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid in individuals with a known allergy/hypersensitivity to mistletoe or to any of its constituents. A life-threatening allergic reaction, called anaphylaxis, occurred after injections of mistletoe.

Most clinical trials were performed with unfractionated extracts, which contain numerous components, and it is difficult to ascribe adverse effects to any component of the mistletoe extracts. Most of the injected administrations of mistletoe may be accompanied by mild manifestations of similar side effects, most of them transient.

The most common reactions reported are erythema (reddening of the skin) and hyperemia (increased blood in an organ). Use of Iscador-M® has resulted in grade 3-4 toxicities (e.g. anorexia, general malaise, depressive moods, fever, and swelling at the site of injection). Other side effects observed have included drug related fever and pain at the site of injection. No drug-related discontinuation or toxic deaths occurred.

Avoid the use of mistletoe with cardiovascular disease, as many adverse effects are possible.

Avoid the use of mistletoe in active/uncontrolled hyperthyroid patients. The manufacturer of Isorel®, Novipharm, notes that mistletoe may additionally activate the patient's already accelerated metabolism and cause over-stimulation, thus worsening the patient's status. Also use cautiously in diabetics as insulin levels may be altered.

Congested intestine, diarrhea, gastroenteritis, nausea, and vomiting have been reported after mistletoe use. Moderate to mild flu-like symptoms, short-term exacerbation of gingivitis, and fever were observed in some patients with subcutaneous administration of mistletoe preparations. Hepatitis has been reported due to ingestion of herbal tablets containing mistletoe and other plant extracts. Elevations of liver enzymes have been reported with high doses of mistletoe.

High urinary frequency/nocturia has been observed. Coma, delirium, fatigue, hallucinations, headaches, pain (generalized, bone, joint), abnormal blood cell counts, pancreas, and kidney damage have been reported along with seizures and sleeplessness. In one clinical study, muscle contracture and muscular pain were reported. Ascites (excess fluid in the abdomen), slowed heart rates, cardiac arrest, dehydration, and high or low blood pressure have also been reported.

Use cautiously in glaucoma patients or in those on cholinergics. Mydriasis (excessive pupil dilation), myosis (excessive pupil constriction), and myalgia (muscle pain) have been reported in clinical study after mistletoe administration. One report exists of eye irritation after the ingestion of mistletoe.

Pregnancy and Breastfeeding

Avoid use of mistletoe in pregnancy and breastfeeding due to the potential uterine stimulant activity of mistletoe.

Mistletoe may increase the effects of blood pressure-lowering medications or have other more serious adverse effects on the heart. Busulphan and mistletoe extract (Helixor®) have been reported to cause organ fibrosis and death.

Use of mistletoe with central nervous system (CNS) depressants may increase sedative effects.

It is unclear if mistletoe interacts with drugs that affect blood sugar levels or drugs used to treat diabetes.

Elevations of liver enzymes have been reported with high doses of mistletoe. Seizure risk may be increased. Seizures have been reported to poison-control centers following the ingestion of crude mistletoe plant material. Immunomodulatory effects have also been proposed.

Theoretically, concomitant use of mistletoe and monoamine oxidase inhibitors (MAOIs) may cause a hypertensive crisis due to mistletoe containing tyramine. Blood sugar levels may be altered by mistletoe. Mistletoe may have negative side effects on the eye and interact with eye drops.

Avoid the use of mistletoe in patients with over-active thyroid glands (a condition called hyperthyroidism). Mistletoe may cause an inflammatory reaction when used in patients with untreated hyperthyroidism.

Interactions with Herbs and Dietary Supplements

The use of garlic, lime tree (Tilia platyphyllos), or hawthorn (Crataegus oxyacantha) with mistletoe may result in additive blood pressure-lowering action.

European mistletoe can have cardiotoxic and negative effects on heart beat strength, cause reflex bradycardia (slow heart rate), and depolarize cardiac muscle. Severe dehydration caused by mistletoe may lead to hypovolemic shock and cardiovascular collapse. Use cautiously with herbs or supplements that alter heart rhythm.

Use of mistletoe with CNS depressants may enhance sedative effects.

Use of mistletoe with cholinergic herbs or supplements may cause increased myosis due to additive adverse effects.

Immunomodulatory effects have been proposed.

Elevations of liver enzymes have been reported with high doses of mistletoe.

Theoretically, the concomitant use of mistletoe and monoamine oxidase inhibitors (MAOIs) may cause a hypertensive crisis due to mistletoe containing tyramine.

It is unclear if mistletoe interacts with herbs or supplements that affect blood sugar levels or agents used to treat diabetes. Avoid the use of mistletoe in hyperthyroid patients. The manufacturer of Iscador® noted mistletoe may cause an inflammatory reaction when used during untreated hyperthyroidism.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.